Previous research has unequivocally demonstrated a reduced capacity of aged rats for the removal of degeneration and for the subsequent reinnervation of the dentate gyrus following unilateral entorhinal lesion. Recently, these findings were correlated with diminished post-lesion glial induction and delayed glial lysosomal activation. In view of the suggested role of hormones in mediating diminished wound healing in the aged animals, it is hypothesized that the altered hormonal status of the aged animal might underlie the reduction in glial response to brain damage. The proposed investigation will examine one aspect of this hypothesis, i.e., whether or not the reported elevation of blood glucocorticoid (GLC) levels in the aged rats contributes to the reduced glial response. Two possible mechanisms of GLC action, i.e., inhibition of glial induction and lysosomal deactivation through nembrane stabilization, will be explored. Young and GLC-treated young adult rats will receive unilateral entorhinal lesions for inducing degeneration in the outer molecular layer of the ipsilateral dentate gyrus. The contralateral side will serve as the control. On 4 and 10 days post-lesion, the rate and the magnitude of glial induction will be evaluated by comparison of the glial cell ratios (cell density on the ipsi-contralateral dentate outer molecular layer) obtained from control and GLC-treated groups of animals. Histochemistry for lysosomal acid phosphatase and Beta-glucuronidase will permit the evaluation of the post-lesion glial lysosomal activation. Changes in the stability of the lysosomes within the denervated zone will be assessed by biochemical estimations of post-lesion changes in the free and total levels of lysosomal enzymes in a mitochondrial-lysosomal fraction of the whole hippocampus. The proposed study will establish whether or not a selective increase in GLC level will inihibit the rate and the magnitude of the glial response to brain degeneration and provide clues to the possible mechanisms of hormone action. Positive correlation between high GLC levels and reduced glial response to degeneration should provide the background for exploring the benefits of adrenalectomy or treatment with anti-GLC agents in ameliorating the reduced repair capacity of the brain in the aged animal.